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The clinical promise of biomarkers of synapse damage or loss in Alzheimer's disease.

Journal article
Authors Martí Colom-Cadena
Tara Spires-Jones
Henrik Zetterberg
Kaj Blennow
Anthony Caggiano
Steven T DeKosky
Howard Fillit
John E Harrison
Lon S Schneider
Phillip Scheltens
Willem de Haan
Michael Grundman
Christopher H van Dyck
Nicholas J Izzo
Susan M Catalano
Published in Alzheimer's research & therapy
Volume 12
Issue 1
ISSN 1758-9193
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Centre for Ageing and Health (Agecap)
Language en
Links dx.doi.org/10.1186/s13195-020-00588...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurochemistry

Abstract

Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD.A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes.

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